Open AccessPotent immunogenicity in BRCA 1 ‐mutated patients with high‐grade serous ovarian carcinoma
Author(s) -
Dai Ying,
Sun Chengdu,
Feng Yi,
Jia Qingzhu,
Zhu Bo
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13678
Subject(s) - immunogenicity , ovarian carcinoma , serous fluid , cancer research , medicine , oncology , serous ovarian cancer , brca mutation , carcinoma , ovarian cancer , biology , immunology , antibody , cancer
Abstract High‐grade serous ovarian carcinomas ( HGSOC s) were among the tumours with an unsatisfactory outcome of immune checkpoint inhibitors ( ICI s). It is imperative to develop feasible biomarker for identifying responsive candidates and guiding precise immunotherapy for HGSOC patients. Here, we analysed genomic data of patients with HGSOC s to depict their immunological phenotype of tumour microenvironment ( TME ) and figure out the major determinants of immunogenicity. In comparison with other solid tumours, we observed the lowest levels of PD ‐L1, total mutation burden ( TMB ) and cytolytic molecules in HGSOC s. Surprisingly, TMB is not certainly positively related to tumour immune response as it failed to predict the response to ICI s in a considerable portion of patients in previous clinical trials. By a machine learning approach in search of biomarkers for immunotherapy implications for HGSOC s, we identified the ten most dominant factors determining the immunogenicity of HGSOC s. Interestingly, we found that BRCA 1 mutated tumours presented a potent immunogenic phenotype, independent of TMB , meeting the criteria of both our dominant factors and the determinants of immunogenicity established before. Our findings provide evidence that BRCA 1‐mutation may be served as a predictive biomarker in guiding ICI therapies for the patients with HGSOC s.